Neuromotor Repertoires in Infants Exposed to Maternal COVID-19 During Pregnancy: a Cohort Study

Overview

Journal BMJ Open

Specialty General Medicine

Date 2023 Jan 23

PMID 36690405

Authors

Viviana Fajardo Martinez

Dajie Zhang

Sophia Paiola

Thalia Mok

Mary C Cambou

Tara Kerin

Rashmi Rao

Patricia Brasil

Fatima Ferreira

Trevon Fuller

Debika Bhattacharya

Suan-Sin Foo

Weiqiang Chen

Jae Jung

Christa Einspieler

Peter B Marschik

Karin Nielsen-Saines

Affiliations

Soon will be listed here.

Abstract

Objective: To evaluate neuromotor repertoires and developmental milestones in infants exposed to antenatal COVID-19.

Design: Longitudinal cohort study.

Setting: Hospital-based study in Los Angeles, USA and Rio de Janeiro, Brazil between March 2020 and December 2021.

Participants: Infants born to mothers with COVID-19 during pregnancy and prepandemic control infants from the Graz University Database.

Interventions: General movement assessment (GMA) videos between 3 and 5 months post-term age were collected and clinical assessments/developmental milestones evaluated at 6-8 months of age. Cases were matched by gestational age, gender and post-term age to prepandemic neurotypical unexposed controls from the database.

Main Outcome Measures: Motor Optimality Scores Revised (MOS-R) at 3-5 months. Presence of developmental delay (DD) at 6-8 months.

Results: 239 infants were enrolled; 124 cases (83 in the USA/41 in Brazil) and 115 controls. GMA was assessed in 115 cases and 115 controls; 25% were preterm. Median MOS-R in cases was 23 (IQR 21-24, range 9-28) vs 25 (IQR 24-26, range 20-28) in controls, p<0.001. Sixteen infants (14%) had MOS-R scores <20 vs zero controls, p<0.001. At 6-8 months, 13 of 109 case infants (12%) failed to attain developmental milestones; all 115 control infants had normal development. The timing of maternal infection in pregnancy (first, second or third trimester) or COVID-19 disease severity (NIH categories asymptomatic, mild/moderate or severe/critical) was not associated with suboptimal MOS-R or DD. Maternal fever in pregnancy was associated with DD (OR 3.7; 95% CI 1.12 to 12.60) but not suboptimal MOS-R (OR 0.25; 95% CI 0.04 to 0.96).

Conclusions: Compared with prepandemic controls, infants exposed to antenatal COVID-19 more frequently had suboptimal neuromotor development.

Citing Articles

The Effect of COVID-19 on Neonatal Outcomes in a Community Hospital.

Martinez-Baladejo M, Kerego Y, Walker A, Ohnona A, Scartelli C, Stoltzfus C J Clin Med. 2025; 14(2.

PMID: 39860424 PMC: 11766128. DOI: 10.3390/jcm14020420.

Deep learning empowered sensor fusion boosts infant movement classification.

Kulvicius T, Zhang D, Poustka L, Bolte S, Jahn L, Flugge S Commun Med (Lond). 2025; 5(1):16.

PMID: 39809877 PMC: 11733215. DOI: 10.1038/s43856-024-00701-w.

Physical development of infants born to patients with COVID-19 during pregnancy: 2 years of age.

Eligulashvili A, Gordon M, Nemerofsky S, Havranek T, Bernstein P, Yee J PeerJ. 2024; 12:e18481.

PMID: 39553723 PMC: 11566510. DOI: 10.7717/peerj.18481.

Feasibility and reliability to assess the motor development of infants exposed to gestational COVID-19 using the Alberta Infant Motor Scale remotely.

Arguelho A, Nazario A, Ribeiro A, Cunha A, Soares-Marangoni D Mhealth. 2024; 10:32.

PMID: 39534456 PMC: 11557160. DOI: 10.21037/mhealth-24-20.

Maternal COVID-19 infection associated with offspring neurodevelopmental disorders.

Duan L, Yin H, Liu J, Wang W, Huang P, Liu L Mol Psychiatry. 2024; .

PMID: 39521839 DOI: 10.1038/s41380-024-02822-z.

References

Shook L, Sullivan E, Lo J, Perlis R, Edlow A . COVID-19 in pregnancy: implications for fetal brain development. Trends Mol Med. 2022; 28(4):319-330. PMC: 8841149. DOI: 10.1016/j.molmed.2022.02.004. View

Ortqvist M, Einspieler C, Aden U . Early prediction of neurodevelopmental outcomes at 12 years in children born extremely preterm. Pediatr Res. 2021; 91(6):1522-1529. DOI: 10.1038/s41390-021-01564-w. View

Darsaklis V, Snider L, Majnemer A, Mazer B . Predictive validity of Prechtl's Method on the Qualitative Assessment of General Movements: a systematic review of the evidence. Dev Med Child Neurol. 2011; 53(10):896-906. DOI: 10.1111/j.1469-8749.2011.04017.x. View

PRECHTL H, Einspieler C, Cioni G, Bos A, Ferrari F, Sontheimer D . An early marker for neurological deficits after perinatal brain lesions. Lancet. 1997; 349(9062):1361-3. DOI: 10.1016/S0140-6736(96)10182-3. View

Benamor Teixeira M, Ferreira Junior O, Joao E, Fuller T, Silva Esteves J, Mendes-Silva W . Maternal and Neonatal Outcomes of SARS-CoV-2 Infection in a Cohort of Pregnant Women with Comorbid Disorders. Viruses. 2021; 13(7). PMC: 8310251. DOI: 10.3390/v13071277. View

Malkova N, Yu C, Hsiao E, Moore M, Patterson P . Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun. 2012; 26(4):607-16. PMC: 3322300. DOI: 10.1016/j.bbi.2012.01.011. View

Kwong A, FitzGerald T, Doyle L, Cheong J, Spittle A . Predictive validity of spontaneous early infant movement for later cerebral palsy: a systematic review. Dev Med Child Neurol. 2018; 60(5):480-489. DOI: 10.1111/dmcn.13697. View

Einspieler C, Bos A, Krieber-Tomantschger M, Alvarado E, Barbosa V, Bertoncelli N . Cerebral Palsy: Early Markers of Clinical Phenotype and Functional Outcome. J Clin Med. 2019; 8(10). PMC: 6833082. DOI: 10.3390/jcm8101616. View

Morgan C, Crowle C, Goyen T, Hardman C, Jackman M, Novak I . Sensitivity and specificity of General Movements Assessment for diagnostic accuracy of detecting cerebral palsy early in an Australian context. J Paediatr Child Health. 2015; 52(1):54-9. DOI: 10.1111/jpc.12995. View

10.

Foo S, Cambou M, Mok T, Fajardo V, Jung K, Fuller T . The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with SARS-CoV-2. Cell Rep Med. 2021; 2(11):100453. PMC: 8549189. DOI: 10.1016/j.xcrm.2021.100453. View

11.

Bosanquet M, Copeland L, Ware R, Boyd R . A systematic review of tests to predict cerebral palsy in young children. Dev Med Child Neurol. 2013; 55(5):418-26. DOI: 10.1111/dmcn.12140. View

12.

Burger M, Louw Q . The predictive validity of general movements--a systematic review. Eur J Paediatr Neurol. 2008; 13(5):408-20. DOI: 10.1016/j.ejpn.2008.09.004. View

13.

Antoun S, Ellul P, Peyre H, Rosenzwajg M, Gressens P, Klatzmann D . Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis. Mol Autism. 2021; 12(1):60. PMC: 8449704. DOI: 10.1186/s13229-021-00464-4. View

14.

Edlow A, Castro V, Shook L, Kaimal A, Perlis R . Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy. JAMA Netw Open. 2022; 5(6):e2215787. PMC: 9185175. DOI: 10.1001/jamanetworkopen.2022.15787. View

15.

Einspieler C, Prayer D, Marschik P . Fetal movements: the origin of human behaviour. Dev Med Child Neurol. 2021; 63(10):1142-1148. DOI: 10.1111/dmcn.14918. View

16.

Zubler J, Wiggins L, Macias M, Whitaker T, Shaw J, Squires J . Evidence-Informed Milestones for Developmental Surveillance Tools. Pediatrics. 2022; 149(3). PMC: 9680195. DOI: 10.1542/peds.2021-052138. View

17.

Reich S, Zhang D, Kulvicius T, Bolte S, Nielsen-Saines K, Pokorny F . Novel AI driven approach to classify infant motor functions. Sci Rep. 2021; 11(1):9888. PMC: 8110753. DOI: 10.1038/s41598-021-89347-5. View

18.

Wang Y, Chen L, Wu T, Shi H, Li Q, Jiang H . Impact of Covid-19 in pregnancy on mother's psychological status and infant's neurobehavioral development: a longitudinal cohort study in China. BMC Med. 2020; 18(1):347. PMC: 7609382. DOI: 10.1186/s12916-020-01825-1. View

19.

Einspieler C, Utsch F, Brasil P, Panvequio Aizawa C, Peyton C, Hasue R . Association of Infants Exposed to Prenatal Zika Virus Infection With Their Clinical, Neurologic, and Developmental Status Evaluated via the General Movement Assessment Tool. JAMA Netw Open. 2019; 2(1):e187235. PMC: 6431234. DOI: 10.1001/jamanetworkopen.2018.7235. View

20.

Einspieler C, PRECHTL H, Ferrari F, Cioni G, Bos A . The qualitative assessment of general movements in preterm, term and young infants--review of the methodology. Early Hum Dev. 1998; 50(1):47-60. DOI: 10.1016/s0378-3782(97)00092-3. View